title: Total synthesis of (-)-cocaine and (-)-ferruginine.
abstract: Total synthesis of tropane alkaloids (-)-cocaine and (-)-ferruginine were accomplished in nine steps each and in 55% and 46% overall yields, respectively, starting from the known Betti base derivative (+)-(7aR,10R,12S)-10-(1H-benzotriazol-1-yl)-7a,8,9,10-tetrahydro-12-phenyl-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazine. In this novel route, RCM reaction and 1,3-dipolar cycloaddition were employed as key steps for the enantioselective construction of tropane skeleton and the regioselective introduction of 3-bromo-2-isoxazoline ring as masked cis-2,3-disubstituents. To obtain the desired precursor (2S,5R)-2-allyl-5-vinylpyrrolidine for RCM reaction, we developed a general and practical method for the preparation of enantiopure cis-2,5-disubstituted pyrrolidines bearing alkene- and/or alkyne-containing substituents. We also offered two highly efficient pathways for the conversion of the 3-bromo-2-isoxazoline ring into the desired cis-2,3-disubstituted groups in (-)-cocaine and (-)-ferruginine.
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Cheng
authors.forename: Xinyan
authors.initials: X
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.forename: Changwei
authors.initials: C
authors.lastname: Shao
authors.forename: Jimin
authors.initials: J
authors.lastname: Xu
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000378:metabolism; D003042:Cocaine / Q000138:chemical synthesis* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D011759:Pyrrolidines / Q000138:chemical synthesis*; D011954:Receptors, Dopamine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000475:Alkenes; D000480:Alkynes; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D011978:Receptors, Nicotinic; D014753:Vinyl Compounds; C418212:ferruginine; D003042:Cocaine